Oxford researchers have identified a new genetic link to chronic pain, in a discovery that could transform treatment strategies.
In a collaborative project between the Nuffield Department of Clinical Neurosciences and the Department of Biochemistry, scientists uncovered that a gene called SLC45A4 is strongly associated with heightened pain sensitivity. Using genetic data from large studies, including UK Biobank and FinnGen, they showed that people carrying variants of this gene reported higher levels of pain.
Further experiments revealed that SLC45A4 encodes the neuronal polyamine transporter—a long-sought molecule responsible for moving polyamines across nerve cells. Polyamines, when present at high levels, are known to overstimulate pain-sensing neurons (nociceptors), leading to chronic pain. By mapping the 3D structure of the transporter with cryo-electron microscopy, the team confirmed its function and demonstrated that mice lacking this gene showed reduced responses to pain stimuli.
Importantly, this work links polyamine regulation directly to chronic pain for the first time, providing a specific molecular target for new pain therapies. Unlike opioids, which bluntly affect many brain pathways and carry risks of addiction, drugs targeting SLC45A4 could reduce pain more safely and effectively.
The findings, published in Nature and supported by Wellcome and the NIHR Oxford Health Biomedical Research Centre, highlight the power of multidisciplinary collaboration, combining neuroscience, biochemistry, structural biology, and genetics. As Professor David Bennett explains, understanding the precise mechanisms of pain is essential for developing new treatments: this discovery not only advances scientific knowledge but also opens the door to innovative, targeted therapies for millions living with chronic pain.
Credit: University of Oxford